This application seeks to establish a graduate training program in Macromolecular Structure and Mechanism at New York University School of Medicine (NYUSOM) leading to a Ph.D. degree. In this post-genomic era, detailed knowledge of macromolecules will lead to a fundamental understanding of information transfer, energy transduction and other basic mechanisms required of all biological systems. The proposed training program will combine early didactic course work, continuous mentorship from thesis committees and advisors with four years of hands-on research to prepare students for independent careers as biomedical scientists. The proposed program would represent a reconfiguration of an existing program in Structural Biology that was initiated 7 years ago with NYUSOM institutional support, namely from the Sackler Institute which oversees all graduate education at NYUSOM. To date, our existing program has graduated five students and currently contains 23 active students at various stages in their graduate studies. Four of these Students are from underrepresented minorities, reflecting the consistently high efforts by the Sackler Institute to increase the numbers and quality of minority applicants to NYUSOM. For the proposed program, we have identified 16 faculty that investigate macromolecular mechanisms using a variety of biophysical, biochemical and structural methods. These faculty can be grouped into four categories based on their research: signal transduction, membrane transport, regulation and assembly of nucleic acids, protein folding and design. These faculty have appointments in several different basic research departments at the School of Medicine and, in addition, in the Biology and Chemistry departments in the Faculty of Arts and Sciences, thus providing a highly interdisciplinary training environment. The proposed curriculum includes 1. specialized courses in the principles and methods of structural and molecular biology, 2. three research rotations, 3. formulation and defense of a research proposal, 4. continuous training and practice in research presentations, 5. discussions and lectures on ethical conduct in science and postgraduate career options, and 6. a rigorous research experience in a participating faculty member's laboratory. RELEVANCE: Detailed information about macromolecules is highly relevant to current trends in healthcare as the genome- wide sequencing gives way to investigations of the mechanisms by which biological systems function. Disease generally results from defects in or attacks on individual macromolecules; given detailed structural information, specific therapeutic agents can be designed to interfere with or ameliorate the consequences.